Ovarian cancer affects 21,000 women each year in the United States and causes death in 13,000. Although platinum-based chemotherapeutic regimens and increased utilization of aggressive cytoreductive surgery have resulted in improved response rates and survival in patients with epithelial ovarian cancer, only 15% to 20% of patients with advanced disease will survive 5 years. This project has as its over-all theme the intensification of initial therapy to improve the response rates and survival in advanced ovarian cancer. A second part of this theme is the investigation of new therapies in patients with recurrent or persistent ovarian cancer and the incorporation of these regiments (when successful) into initial therapeutic trials. Specific aims are: 1) the evaluation of a coordinated program of ultra-intense intravenous chemotherapy (with stem cell support), interval cytoreductive surgery and intraperitoneal therapy in untreated patients with advanced epithelial ovarian cancer, 2) the evaluation in untreated patients of the comparative efficacy of conventional surgery and chemotherapy versus the multimodal therapy utilizing intense intravenous chemotherapy, interval cytoreductive surgery and intraperitoneal chemotherapy, 3) the generation of computer models for the treatment of ovarian cancer based on prior experience in modeling breast cancer therapy to validate the models against prior experience, 4) the evaluation of consolidation therapy in patients with a negative second-look laparotomy, 5) the evaluation of new drugs approaches to systemic therapy in patients with refractory ovarian cancer including new drugs which may be active in platinum/taxol resistant ovarian carcinoma and methods for reversing or preventing drug resistance, and 6) the evaluation of new approaches to regional therapy in patients with refractory ovarian cancer including new drugs, new drug combinations and the use of radiolabeled monoclonal antibodies. This comprehensive program to improve the therapy of ovarian cancer is possible because of our large patients population and the close collaboration of the members of the various projects and cores in this program project.